中文摘要：

目的检测PARP抑制剂维利帕尼（veliparib）与抗癌药物多柔比星（doxorubicin）联合应用对肝癌耐药细胞株BEL-7404增殖抑制的作用。方法以BEL-7404细胞为研究对象,常规培养传代,经多柔比星和（或）维利帕尼处理24h后,通过四甲基偶氮唑盐（MTT）比色法观察细胞的增殖率变化,采用流式细胞术Annexin V-FITC/PI双染法分析细胞凋亡水平,通过单细胞凝胶电泳实验评价DNA损伤程度,通过聚丙烯酰胺凝胶电泳（Western blotting）法检测细胞线粒体和胞浆中细胞色素c水平变化。结果多柔比星和维利帕尼联合应用组的细胞增殖率明显低于对照组和多柔比星单独处理组（P〈0.01）,细胞凋亡率则显著高于对照组和多柔比星单独处理组（P〈0.05）;同时,多柔比星和维利帕尼联合应用组细胞DNA损伤水平较对照组和多柔比星单独处理组明显加重（P〈0.01）,而细胞色素c在胞浆中的水平则显著高于对照组和多柔比星单独处理组（P〈0.01）。结论维利帕尼与多柔比星联合作用可以抑制BEL-7404细胞的增殖,并诱导细胞DNA损伤和凋亡,其机制与胞浆中细胞色素c的表达升高有关。

英文摘要：

Objective The aim of this study was to irlvestigate the combined effects of veliparib and doxorubicin on the prolifer- ation and apoptosis of human hepatocdlular carcinoma cell line BEE - 7404. Methods BEL - 7404 cells were taken as the ob- ject of study and conventional culture was performed. The cells were treated with doxorubicin and/or veliparib for 24h. Cell proliferation were detected by MTT assay. DNA damage and cell apoptosis were measured by comet assay and flow cytometry using annexin V - FITC/PI staining respectively. The expression of cytochrome c in the mitochondrion and cytoplasm was detected byWestern blotting. Results Compared with the control group and doxorubicin- treated group, the cell proliferation rate in the combined- treatment group was significantly lower（ P 〈 0.01 ）, while the cell apoptosis rate was significantly higher（ P 〈 0.05 ）. Furthermore, the DNA damage in the combined- treatment group was more serious and the expression of cytochrome c in cyto- plasm was upregulated（P 〈 0.01）. Conclusions Combined treatment of veliparib and doxombicin can inhibit proliferation and induce DNA damage and apoptosis in BEL - 7404 cells. The mechanism probably involves increased intracellular cytochrome c expression